We introduce a unique microfluidic-based approach for the
high-throughput non-destructive assaying of cells without the need for
specific labels or reagents. Based on measurement of both static and
dynamic cell mechanical properties using applied optical forces, we will
apply this technique (known as “optical stretching”) in a high-speed
high-throughput manner. To date, optical stretching has been used only
on small cell numbers; however, highintensity, microscale laser sources
and the integration of these within dynamic microfluidic systems has
enabled our proposed approach. In this, fully integrated optical-based
sensors and mechanical stretchers will be used to identify and, upon
demand, isolate single cells. Once identified, such targeted cells can
then be transported on-chip to culture chambers within the device or for
dispensing into standard bio-laboratory instrumentation for off-chip
analysis. Though there is broad need, our proposed technology will be
tested and developed using malaria parasite infected red blood cells as
the target cell. This work will be done in collaboration with the
Laboratory of Malaria and Vector Research at the NIAID. Our aims
include: Aim 1: Mechanical Property Detection and Interpretation. We
will employ optical manipulation methods integrated within microfluidic
systems for label-free, non-destructive cell mechanical property
measurement. Modeling approaches will be developed for both
interpretation of applied force/deformation experimental data and for
device design. Here, malaria-infected red blood cells will provide a
good model target since cell stiffness changes dramatically during
parasite development. Demonstrating greatly simplified device designs
and associated ease-of-use, we will install an instrument in an active
NIH laboratory. Aim 2: Optical Manipulation for Cell Identification and
Isolation. We will integrate optical methods within microfluidic systems
for single cell detection and manipulation. Here, methods for both
on-chip cell isolation and off-chip isolation will be developed and used
to improve our installed NIH protototype. Aim 3: High Throughput
Mechanical Testing. To achieve high-throughputs, modified microfluidic
and faster detection techniques will be required. In this phase, the
coupling of hydrodynamic and optical forces will be explored to improve
device performance. In addition, time-varying optical forces will be
employed to identify optimal signal response and dynamic physical
properties.